Prostate Surgery

Jeremy Grummet is a Urological Surgeon with particular expertise in urological cancer. He has been instrumental in the introduction of transperineal prostate biopsy as an alternative to transrectal biopsy, to reduce infection rates after biopsy. Jeremy is conducting multiple clinical research projects on prostate biopsy and heads the Victorian Transperineal Biopsy Collaboration (VTBC) research group. In this article, Jeremy discusses the techniques and advantages of transperineal biopsy.

What’s wrong with the current standard method of prostate biopsy?

A biopsy is where a sample of tissue is taken for examination under a microscope, usually to determine if cancer is present. As you can see from the diagram below, the easiest way to access the prostate is via the rectum. That’s why we perform a rectal examination - so we can feel the back of the prostate for any suspicious lumps. Most prostate cancers are located towards the back of the prostate (peripheral zone), so a transrectal ultrasound-guided (TRUS) biopsy is a convenient way of sampling this area. Typically, at least 12 cores of tissue are taken during a TRUS biopsy.

The other advantage of the TRUS biopsy is that it can be performed in just a few minutes by giving the patient intravenous sedation or using a local anaesthetic nerve block.

However, passing the needle of the biopsy gun through the wall of the rectum multiple times is problematic. As you’d expect from an organ that stores faeces, the rectum has a high concentration of bacteria. These bacteria don’t cause any problems as long as they stay in the rectum. However, passing the biopsy needle through the wall of the rectum allows these bacteria to access the prostate and its rich blood supply. This in turn can lead to a serious infection in the blood called septicaemia (sepsis). Septicaemia makes patients feel very unwell, requires hospitalization for intravenous antibiotic therapy, and can even be life-threatening.

This risk of sepsis in TRUS biopsy is well-recognised. It is therefore standard to use an antibiotic to help prevent such an infection. Unfortunately, the antibiotic doesn’t always work, so there is still a risk of sepsis, which has been measured at about 1-2%.

Today, there is the additional and growing problem of bacteria developing antibiotic resistance. This has been reported worldwide and was the subject of a major US Government report last year.

Our own research group, the Victorian Transperineal Biopsy Collaboration (VTBC), reviewed the scientific literature, finding that developing resistance is a particular problem for bacteria that live in the rectum, so that the antibiotics we would normally use, such as ciprofloxacin, can sometimes be rendered ineffective. This coincides with reports of increasing rates of TRUS biopsy sepsis even as high as 5%.

Our research has also found that, as a result of the above, some Australian and New Zealand urology practices have resorted to using big-gun broad-spectrum antibiotics on a regular basis to prevent TRUS biopsy sepsis. Whilst this may reduce sepsis for the individual patient, from a public health perspective, it is a step backwards, as widespread use of such antibiotics will lead to even more resistance. Unfortunately, we are already seeing this happening, with hospitals in Australia finding CRE (Carbapenem-Resistant Enterococci) in their wards.

What is transperineal biopsy, and why is it safer?

Fortunately, there is another approach to prostate biopsy which avoids perforation of the rectum altogether. Instead, the biopsy needle can be passed via the skin of the perineum. In men, the perineum is the part of the body between the scrotum and the anus.

As shown in the diagram, the ultrasound probe is still passed into the rectum to provide an image of the prostate. But instead of the biopsy needle passing alongside the probe, it is passed through a grid, which itself is fixed against the probe outside the body. Prior to insertion of the ultrasound probe, the perineal skin is easily prepared in a sterile fashion, just as any other incision site is prepared before surgery to prevent wound infection. (Although worthwhile attempts have been made to sterilize the rectum, this has not been possible.)

Our group studied the experience of transperineal (TP) biopsy around the world and found that in over 6,600 patients, there were only 5 patients re-admitted to hospital for sepsis - a rate of just 0.076%, or less than 1 in a thousand. Furthermore, in our own published experience of 245 TP biopsies our rate of re-admission for infection was zero. (We have now performed over 400 TP biopsies, still without a single episode of infection.)

Based on the published scientific evidence to date then, it appears that TP biopsy is a safer option than TRUS biopsy due to its near-zero sepsis risk. It also gives the advantage of avoiding regular use of heavy-duty antibiotics, thereby avoiding promotion of resistant bacteria, now labelled by the US Government Center for Disease Control as a Serious Threat to population health worldwide. As a result, we now use TP biopsy routinely for all prostate biopsies.

Are there any downsides to the transperineal approach?

Looking at the diagram above, you would expect TP biopsy to be painful, which is why it is typically performed under a general anaesthetic (although methods of using local anaesthetic only have been reported). We routinely perform TP biopsy under GA. As a result, men experience no pain during the procedure, and very little afterwards, so that paracetamol is only required occasionally. Although a general anaesthetic is required, it is of a short duration only (less than 30 minutes) and is very safe.

Practitioners of TP biopsy initially reported a higher risk of acute urinary retention (unable to pass urine) with this approach. However, with further experience, and by deliberately avoiding the area around the urethra, this rate dropped so that it is now similar to the risk seen in TRUS biopsy (around 2%). Although a catheter has been used by some doctors, as shown in the diagram above, it is unnecessary.

Due to anecdotal experience, some urologists have been concerned that TP biopsy may lead to erectile dysfunction by damaging the erectile nerves or to more difficult surgery if cancer is found and the prostate needs to be removed. However, evidence to date, albeit scant, does not support either of these concerns.

Is it as good as TRUS at cancer detection?

According to the scientific literature, TP biopsy is at least equivalent to TRUS biopsy in its ability to detect cancer. Some research has also found improved detection of cancers at the front of the prostate (anterior). This may be due to the typically easy access TP biopsy provides to all areas of the prostate, particularly anteriorly. Conversely, it can often be difficult to reach the anterior prostate via TRUS biopsy, especially in large glands.

What other advantage might TP biopsy provide?

In TP biopsy, the ultrasound probe is stabilized by equipment that is fixed to the operating table. The grid through which the biopsy needle is passed is, in turn, stabilized against the ultrasound probe. This set-up permits accurate and reproducible biopsy needle placement.

In the past, TP biopsies were taken in a systematic fashion only, evenly sampling various areas of the prostate. Whilst this is still performed routinely, in addition we are now often performing targeted biopsies of suspicious lesions if found on a prostate MRI. The stable arrangement of TP biopsy therefore permits accurate targeting of such lesions, with the potential to further improve the accuracy of cancer detection.

The first guest blog for February is by Jim Duthie, a Urologist in Tauranga, New Zealand. Jim has written two Apps to make it easier for patients to be actively involved in their prostate cancer management. One app helps track PSA over time along with a history of prostate biopsies and treatments. The other greatly helps consolidate treatment for patients who are on ADT (hormone treatment).

For any question, the clichéd answer is now “There’s an App for that”, referring to the ubiquitous mobile applications for smartphones that seem to solve many of our problems, real or imagined. For medical conditions, this is increasingly the case. The “Medical” category is currently the most rapidly growing domain in the Apple App store. You can now download anything from a nomogram for predicting your risk of heart disease, to the somewhat questionable App that can treat whatever ails you by using your iPhone torch as a form of phototherapy. For me, designing mobile Apps was an effective solution for specific problems facing Urology patients.

Androgen Deprivation Therapy App

The process began with a concern that men undertaking Androgen Deprivation Therapy (ADT) were poorly followed up in terms of the myriad potential side effects that this treatment causes, from bone density to dyslipidaemia, to depression, and hot flushes. It is unclear exactly how many men are receiving ADT, let alone what percentage receive adequate follow up care. As Urologists, we are not experts in managing the complexities of, for example, cardiac risk factors.

Despite best intentions, we also lack the time and expertise to manage depression and cognitive impairment. It makes sense for General Practicioners/Family Physicians (GPs/FPs) to coordinate this follow up, but the physiological effects may seem complex and intimidating for a non-specialist. Perhaps Endocrinologists may be better equipped, but not from the point of view of coordinating patient management, and again a GP/FP usually has a better understanding of psychosocial issues. With this lack of clarity around responsibility it is easy for uncomplaining patients to slip through the cracks.
In practice, men receiving ADT may only attract medical attention after suffering a significant complication of their treatment.

To improve this situation, I considered that a centralized ADT database where men are recruited at the time of initiation of therapy, then sent reminders at regular follow up intervals would be ideal, and could additionally provide a bank of men available for clinical trials and retrospective study. Unfortunately, database creation and management is prohibitively expensive, and despite my best efforts such a structure is some way off yet.

I identified the core follow up issue as being getting the right investigations performed at the right time. To achieve this GPs/FPs need to be aware of the necessary tests, and patients informed about when to see their doctor for follow up. The ADT App attempts to achieve this with automated “push notifications” (alerts appearing on the smartphone) when they are due to see their GP, as well as listing recommended investigations according to the elapsed time since commencing treatment. The patient can also read about potential side effects by body system, and follow links for explanations about why the specific tests are required in terms of the physiological effects of androgen deprivation. This is an App aimed at patients, however the intention is that a GP/FP could also have this on their phone as a reference and educational aid.

PSA Manager App

This App addresses a broader group, any man either undertaking prostate cancer treatment or PSA screening. The idea of a “PSA Tracker” is not new. Before the advent of iTunes I encountered a retired accountant who had graphed his PSA over time by hand. An electronic equivalent is easy to achieve, but does it add much to the patient’s care? I thought that an “all in one” manager for prostate cancer screening and treatment would be more useful. The PSA Manager App allows the input of results of prostate biopsies, dates and modalities of treatment for cancer and benign prostate disease including surgery, radiation, and newer novel techniques, and results of imaging investigations such as CT, MRI, or bone scans with a facility for entering a free-text description of the results of these. The data are then presented on a graph with colour-coded markers to represent the timing of the interventions. PSA velocity and doubling time can also be calculated. The intention is to allow men a clear overview of their PSA changes during screening, and if applicable, the evolution and treatment of their prostate cancer.

Identifying barriers to care is an essential part of equitable health delivery, and something I considered at length. The first challenge I identified for men using these Apps, particularly the ADT App, was advanced age. We may think of men on ADT as being elderly, perhaps frail, and probably not expert in using technology. Firstly, this perception ignores the group of men receiving ADT as neoadjuvant/adjuvant treatment for radiation therapy, which constitutes a younger and healthier cohort of men. Secondly, many ADT patients attend clinic with a younger family member, and my experience has been that when I ask if anyone in the family has an iPod, iPad, or iPhone, the answer is usually yes. As long as one tech-savvy person can enter the data, the Apps work well by proxy.
In designing the interface, details such as larger buttons to suit male fingers and presbyopic vision were considered.

Finally, any financial cost will constitute a barrier to some patients. The solution was the make the Apps free to download. This meant securing funding which was generously provided by unrestricted grants from Australian Prostate Cancer Research and Ipsen for the ADT and PSA Manager Apps respectively. Although I receive no reimbursement from the development of either App, I believe patients feel more confident in a product provided solely for their benefit, and I can promote the Apps to them and my colleagues with no financial conflict of interest.

This week's guest post is by Dr. Charles Chabert, a urologist based on The Gold Coast, QLD, Australia. He specialises in minimally invasive treatment options for diseases of the prostate gland, and has extensive experience in laparoscopic, robotic and laser (greenlight) surgery. He discusses a new treatment for bladder outflow obstruction caused by prostate enlargement.

Urolift®- A new option for the management of Urinary Symptoms related to benign prostate enlargement.

Urolift® is a new minimally invasive treatment for men who suffer urinary symptoms related to BPH (benign prostatic hyperplasia or prostate enlargement). UroLIft has been studied internationally for the last 5 years and the initial data look very promising. The first UroLift implants in Queensland, were performed at Pindara Private Hospital, on 31st August 2013.

The UroLift system opens the prostatic urethra (the pipe which passes through the centre of the prostate) thus relieving obstruction. The system involves the insertion of small permanent implants, which are placed with the aid of a cystoscope or small camera. The implants work by pulling the lateral lobes (sides) of the prostate outwards, creating a passage in the middle of an obstructed prostate.

Traditionally, treatments for BPH have included medications or surgery. Commonly used medications include alpha blockers or 5-alpha reductase inhibitors alone or in combination. Side effects with these medications include a stuffy nose, dizziness, and sexual dysfunction. In addition, inadequate relief from urinary symptoms prompts many men to discontinue treatment early and progress to surgical intervention.

The UroLift® System was launched in Australia in 2013, aiming to bridge the gap in prostate treatments by offering a minimally invasive alternative that provides for rapid and durable relief that is 2 to 3 times that of medication, without the complications of surgery. A unique feature is that the UroLift® system preserves sexual function, as demonstrated in clinical studies.

In 2011 a multi-national randomised study was conducted to validate the early results. All primary endpoints were met, and the UroLift® system again demonstrated meaningful improvement in symptoms and quality of life without the introduction of sexual dysfunction or surgical complications.

To date nearly all treatments for BPH (benign prostatic hyperplasia) have focused on removing, destroying or chemically altering what is, by definition, benign tissue. The Prostatic Urethral Lift (PUL) was developed under the innovative premise that symptoms can be improved without injuring the prostate.